Low levels of emphysema burden on LDCT and spirometry-based OLD: Joint Effects on Mortality

Theprognostic value of low levels of CT-defined emphysema and their interaction with obstructive lung disease (OLD) remains unclear.

Does emphysema, as defined by low-attenuation areas (LAA-₉₅₀) on CT, confer differential mortality risk according to the presence of airflow limitation?

We included 5,276 adults who underwent low-dose CT and spirometry between 2010 and 2019. Mortality was ascertained through linkage with national death records. Cox models estimated hazard ratios (HRs) for mortality according to LAA-₉₅₀ and OLD. Dose-response relationships were assessed using restricted cubic splines, and progression was evaluated among participants with low baseline emphysema.

Among 5,276 adults in a health-screening cohort, 66.3% were men and 47.2% were ever smokers. Over a median follow-up of 12.9 years, LAA-950 ≥1.5% alone (HR 1.32, 95% CI 0.85 to 2.06) and OLD alone (HR 0.95, 95% CI 0.50 to 1.80) were not associated with mortality. Their combination increased risk (HR 3.10, 95% CI 1.77 to 5.42; p for interaction = 0.04). A graded association between emphysema and mortality was observed only in individuals with OLD. In stratified analyses, emphysema was associated with mortality in never smokers without OLD, whereas a joint effect was observed in ever smokers. Among participants with LAA-950 <1.5%, progression to ≥1.5% increased mortality in those with OLD (HR 3.97, 95% CI 1.23 to 12.90), but not in those without OLD.

Low-level CT-defined emphysema was associated with higher all-cause mortality mainly when accompanied by spirometry-defined OLD. These findings suggest that low-level LAA-₉₅₀ may have greater prognostic relevance in the presence of airflow limitation.